Barrett esophagus, or Barrett metaplasia, describes the phenotypic change of normal esophageal squamous epithelium to a columnar and intestinal-type epithelium. This metaplastic change is important because patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The ... Barrett esophagus, or Barrett metaplasia, describes the phenotypic change of normal esophageal squamous epithelium to a columnar and intestinal-type epithelium. This metaplastic change is important because patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett metaplasia is gastroesophageal reflux (GER; 109350). The retrograde movement of acid and bile salts from the stomach into the esophagus in this disease causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes (summary by Wong et al., 2005).
Barrett (1950) described a patient with chronic ulcerating esophagitis in which columnar rather than squamous epithelium surrounded the ulcers. Allison and Johnstone (1953), followed by many others, showed that the columnar epithelium-lined intrathoracic structure is anatomically and functionally ... Barrett (1950) described a patient with chronic ulcerating esophagitis in which columnar rather than squamous epithelium surrounded the ulcers. Allison and Johnstone (1953), followed by many others, showed that the columnar epithelium-lined intrathoracic structure is anatomically and functionally esophagus. The proximal esophagus usually retains its normal squamous epithelium. The Barrett esophagus is a complication of gastroesophageal reflux. Why it develops only in some patients is not clear; Sjogren and Johnson (1983) suggested that it 'may be congenitally determined in part.' Familial occurrence was reported by Borrie and Goldwater (1976). Adenocarcinoma of the esophagus has an incidence of about 10% in the Barrett esophagus. Adenocarcinoma constitutes a minority of esophageal cancers but most of these originate in a Barrett esophagus.
In a study of 116 patients of European descent with Barrett esophagus and/or esophageal adenocarcinoma, Orloff et al. (2011) identified rare germline mutations in 3 different genes. Candidate genomic regions were studied after being identified by genomewide linkage ... In a study of 116 patients of European descent with Barrett esophagus and/or esophageal adenocarcinoma, Orloff et al. (2011) identified rare germline mutations in 3 different genes. Candidate genomic regions were studied after being identified by genomewide linkage analysis of 21 concordant and 11 discordant sib pairs with the disorders. A mutation in the MSR1 gene on chromosome 8p22 (R293X; 153622.0001) was found in 8 (6.9%) patients in the initial cohort and in 2 (3.4%) of 58 patients in a replication study. A second MSR1 mutation (L254V; 153622.0003) was found in 2 patients (1.7%) in the initial cohort. A mutation in the CTHRC1 gene on 8q22 (Q44P; 610635.0001) was found in 1 (1.1%) patient in the initial cohort and in 1 (1.7%) in the replication cohort, and a mutation in the ASCC1 gene on 10q22 (N290S; 614215.0001) was found in 2 (2.1%) patients in the initial cohort. - Associations Pending Confirmation The Esophageal Adenocarcinoma Genetics Consortium and Wellcome Trust Case Control Consortium (2012) presented the first genomewide association study of Barrett esophagus susceptibility comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at 2 loci were associated with disease risk: dbSNP rs9257809 on chromosome 6p21, within the MHC locus (combined p = 4.09 x 10(-9); OR = 1.21; 95% CI, 1.13-1.28); and dbSNP rs9936833 on chromosome 16q24 (combined p = 2.74 x 10(-10); OR = 1.14; 95% CI, 1.10-1.19). The SNP dbSNP rs9936833 resides 141 kb centromeric to FOXF1 (601089), a forkhead transcription factor in the hedgehog signaling pathway that has a role in the development of the gastrointestinal tract and has been reported to cause esophageal structural alterations when inactivated. The region around dbSNP rs9936833 contains multiple binding sites for specific transcription factors, such as FOXP2 (605317), that control FOXF1 expression. The SNP dbSNP rs9257809 lies on the telomeric edge of the MHC region.